Naringenin-loaded PCL nanoparticles attenuate glial activation and TNF-α expression in iron-induced post-traumatic epilepsy

Post-traumatic epilepsy (PTE) is the cosequence of traumatic brain damage (TBI), which poses an important health risk for the human population. The underlying mechanism of PTE is complex and appears to be linked to various cellular processes, including oxidative stress and neuroinflammation. Over the years, several studies have reported that most of the available antiseizure medicines are ineffective in preventing PTE. As a result, there is an urgent need to search for alternative treatment options. Naringenin is a flavonoid with multiple pharmacological properties and has shown beneficial effects in several health issues, including neurological disorders. In this study, we investigated the effect of naringenin-loaded PCL nanoparticles (NarNPs) on neuroinflammatory responses in a PTE model. NarNPs were produced using the nanoprecipitation method, and their physicochemical properties were comprehensively examined. To induce epilepsy, FeCl₃ was injected intracortically to rats and naringenin (both free naringenin (NAR) and NarNPs) was administered orally 15 days post-surgery. Epileptic seizures were observed by electroencephalography (EEG) patterns and spectral power analysis of γ-waves. Immunofluorescence analysis was conducted to explore the disease-modifying potential of NarNPs. Our findings demonstrated that NarNPs distinctly reduced epileptiform seizure activity in epileptic rats. The study found that NarNPs lowered the expression of GFAP, IBA1, and TNF-α. The observed ameliorative effects were more pronounced in NarNP-treated rats than in the NAR-treated group. Overall, our data imply that NarNPs have significant antiseizure and disease-modifying potential by attenuating glial activation and TNF-α production in PTE rats.